Production of L-Isoleucine by AHV Resistant Mutants of Brevibacterium flavum

The growth of Brevibacterium flavum No. 2247A was inhibited by α-amino-β-hydroxy-valeric acid (AHV), and the inhibition was partially reversed by L-isoleucine.

AHV resistant strain ARI-129, which was isolated on a medium supplemented with 2 mg/ml of AHV, produced 11 g/liter of L-isoleucine.

No difference was observed in threonine dehydratase between No. 2247A and ARI–129. Homoserine dehydrogenase from ARI–129 was insensitive to the feedback inhibition by L-isoleucine and L-threonine.

O-Methyl-L-threonine resistant mutant, strain AORI–126, which was derived from ARI–129, produced 14.5 g/liter of L-isoleucine. Specific activity of threonine dehydratase from AORI–126 increased about two-fold higher than those from No. 2247A and ARI–129, whereas degree of inhibition of the enzyme by L-isoleucine was the same among three strains.

Among auxotrophic mutants derived from ARI–129, adenine and lysine auxotrophs produced more L-isoleucine than the parent did.

In the adenine auxotroph, L-isoleucine production was markedly reduced by the addition of excess adenine.